title: Clinical relevance of decreased free protein S levels: results from a retrospective family cohort study involving 1143 relatives.
abstract: Conflicting data have been reported on the risk for venous thrombosis in subjects with low free protein S levels. We performed a post-hoc analysis in a single-center retrospective thrombophilic family cohort, to define the optimal free protein S level that can identify subjects at risk for venous thrombosis. Relatives (1143) were analyzed. Relatives with venous thrombosis (mean age 39 years) had lower free protein S levels than relatives without venous thrombosis (P < .001), which was most pronounced in the lowest quartile. Only relatives with free protein S levels less than the 5th percentile (< 41 IU/dL) or less than the 2.5th percentile (< 33 IU/dL) were at higher risk of first venous thrombosis compared with the upper quartile (> 91 IU/dL); annual incidence 1.20% (95% confidence interval [CI], 0.72-1.87) and 1.81% (95% CI, 1.01-2.99), respectively; adjusted hazard ratios 5.6, (95% CI, 2.7-11.5) and 11.3 (95% CI, 5.4-23.6). Recurrence rates were 12.12% (95 CI, 5.23-23.88) and 12.73% (95% CI, 5.12-26.22) per year; adjusted hazard ratios were 3.0 (95% CI, 1.03-8.5) and 3.4 (95% CI, 1.1-10.3). In conclusion, free protein S level can identify young subjects at risk for venous thrombosis in thrombophilic families, although the cutoff level lies far below the normal range in healthy volunteers.
authors.affiliation: Division of Haemostasis, Thrombosis and Rheology, Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands. w.lijfering@int.umcg.nl
authors.forename: Willem M
authors.initials: WM
authors.lastname: Lijfering
authors.forename: Rene
authors.initials: R
authors.lastname: Mulder
authors.forename: Min Ki
authors.initials: MK
authors.lastname: ten Kate
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.forename: Andre B
authors.initials: AB
authors.lastname: Mulder
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meer
mesh_terms: D000293:Adolescent; D015331:Cohort Studies; D005190:Family; D006801:Humans; D015994:Incidence; D017293:Protein S / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D020246:Venous Thrombosis / Q000209:etiology / Q000378:metabolism*
chemical_list: D017293:Protein S